The Stille reaction in the synthesis of the C37-norcarotenoid butenolide pyrrhoxanthin. Scope and limitations

Article abstract of DOI:10.1021/jo060490z

The sequential Stille cross-coupling reactions of the dihalogenated γ-alkylidenebutenolide 7 with stannanes 9 and 6 afforded the carbon skeleton of pyrrhoxanthin, a highly functionalized C7′-C8′ acetylenic C₃₇-norcarotenoid butenolide. Although

Full text of DOI:10.1021/jo060490z

The Stille Reaction in the Synthesis of the C37-Norcarotenoid
Butenolide Pyrrhoxanthin. Scope and Limitations
Bele´n Vaz, Marta Dom´ınguez, Rosana AÄ lvarez, and Angel R. de Lera*
Departamento de Qu´ımica Orga´nica, Facultade de Qu´ımica, UniVersidade de Vigo,
Lagoas Marcosende, E-36310, Vigo, Spain
qolera@uVigo.es
ReceiVed March 7, 2006
The sequential Stille cross-coupling reactions of the dihalogenated γ-alkylidenebutenolide 7 with stannanes
9 and 6 afforded the carbon skeleton of pyrrhoxanthin, a highly functionalized C7′-C8′ acetylenic C37-
norcarotenoid butenolide. Although the first halogen-selective Stille coupling takes place in 90% yield
at ambient temperature, double isomerization of the Z,E- to the E,Z-C7′-C10′ enyne, likely induced by
the catalyst, accompanyied the bond formation, leading to 9′Z-20 and, ultimately, to 9′Z-pyrrhoxanthin
9′Z-1.
Introduction
Pyrrhoxanthin 11 is a naturally occurring C37-norcarotenoid
characterized by having a structural truncation on the polyene
chain and an abnormal arrangement of methyl groups relative
to parent C40-carotenoids.2 Isolated from microalgae and
planktonic dinoflagellates responsible for “red tide” episodes,
its structure was elucidated by Liaaen-Jensen and co-workers.3
With a similar skeleton up to C8′ (Figure 1), pyrrhoxanthin 1
contains an enyne in place of the allenol moiety of congener
peridinin 2 and is therefore included in the C7′-C8′ acetylenic
carotenoid group. As in peridinin 2, a polyene chain of all-
trans geometry comprising a γ-alkylidenebutenolide ring con-
nects two highly oxygenated cyclohexenyl end groups decorated
with 4 stereocenters.
FIGURE 1. Representative C37-norcarotenoid butenolides isolated from
planktonic dinoflagellates with the IUPAC carotenoid-specific number-
ing.
* To whom correspondence should be addressed. Fax: 34986811940.
(1) Johansen, J. E.; Svec, W. A.; Liaaen-Jensen, S.; Haxo, F. T.
Phytochemistry 1974, 13, 2261.
Particularly challenging to synthetic chemists is the control
of the relative and absolute configurations of the stereogenic
elements of these C37-norcarotenoids not only during the
preparation of all required fragments but also in the assembly
of the entire carotenoid structure. Not surprisingly, only one
synthesis of racemic pyrrhoxanthin 1 has been reported to date.4
(2) For recent monographs, see the following: (a) Britton, G., Liaaen-
Jensen, S., Pfander, H., Eds.; Carotenoids. Part 1A. Isolation and Analysis;
Birkha¨user: Basel, Germany, 1995. (b) Britton, G., Liaaen-Jensen, S.,
Pfander, H., Eds.; Carotenoids. Part 1B. Spectroscopy; Birkha¨user: Basel,
Germany, 1995. (c) Britton, G., Liaaen-Jensen, S., Pfander, H., Eds.;
Carotenoids. Part 2. Synthesis; Birkha¨user: Basel, Germany, 1996.
(3) (a) Johansen, J. E.; Borch, G.; Liaaen-Jensen, S. Phytochemistry
1980, 19, 441. (b) Aakermann, T.; Liaaen-Jensen, S. Phytochemistry 1992,
31, 1779.
(4) a) Yamano, Y.; Ito, M. J. Chem. Soc., Perkin Trans 1 1993, 1599.
(b) Ito, M.; Hirata, Y.; Tsukida, K.; Tanaka, N.; Hamada, K.; Hino, R.;
Fujiwara, T. Chem. Pharm. Bull. 1988, 36, 3328.
10.1021/jo060490z CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/01/2006
5914
J. Org. Chem. 2006, 71, 5914-5920

C37-Norcarotenoid Butenolide Pyrrhoxanthin
FIGURE 2. Key condensation step of the synthesis of rac-pyrrhoxanthin 1 reported by Ito et al.
FIGURE 3. Approach to 6′-epi-peridinin 5 using the Julia-Stille-Stille sequence.
In his approach to highly functionalized C37-norcarotenoid
butenolides, Ito assembled the entire skeleton of pyrrhoxanthin
1 using a classical Julia reaction between aldehyde 3 and allyl
phenyl sulfone 4. This critical step (Figure 2), which also
constructed the butenolide ring of rac-1, proved inefficient (13%
yield of a 50:50 mixture of the 11E/11Z γ-alkylidenebutenolide
isomers). This limitation and additional drawbacks found along
the synthetic sequence call for novel, more efficient routes to
these complex natural products.
Metal-catalyzed cross-coupling reactions are undoubtedly a
method of choice for C-C bond formation, particularly for the
connection of unsaturated fragments. In the carotenoid field,
novel approaches to symmetrical C40 compounds using orga-
nozinc (Negishi coupling)5 or organotin (Stille coupling)6
derivatives and their halogenated polyenyl counterparts assisted
by palladium have been disclosed. In addition, we recently
reported the application of the Stille coupling to the construction
of three key bonds of allenic C37-norcarotenoids, including the
last two connective steps that assembled the skeleton of 6′-epi-
peridinin 5 (Figure 3).7 We noticed, gratifyingly, a selective
and efficient Z to E isomerization of the C11′-C12′ olefin (itself
obtained stereoselectively by a Julia-Kocienski reaction) under
the quite drastic coupling conditions required for the last Stille
coupling (the C8-C9 bond formation), which set the correct
geometry of the final C37-norcarotenoid.8 This was in retrospect
a fortunate outcome since Z isomers of the C11′-C12′ double
bond proved to be more stable than the corresponding E
counterparts, and polyene degradation was minimized along the
sequence.
Given the fact that enantiopure pyrrhoxanthin 1 has not
yielded to synthesis, and that the Julia-Stille-Stille approach
to 6′-epi-peridinin 5 depicted in Figure 3 appears versatile and
therefore suitable for this endeavor, we decided to include this
C7′-C8′ acetylenic carotenoid in our synthetic program. We
hereby validate the above approach as a highly efficient route
to the C37-norcarotenoid butenolides. However, we also show
an additional limitation of palladium-catalyzed cross-coupling
processes applied to the synthesis of highly functionalized
carotenoids, namely, the thus far unavoidable double isomer-
ization of the C7′-C10′ enyne fragment which occurred at the
stage of the advanced intermediate 20.
Results and Discussion
The presence of a common γ-alkylidenebutenolide system
with additional conjugation through the CR-position in these
natural C37-norcarotenoids called for the use of a common
central dihalogenated C8-butenolide unit 7 as a linchpin.9 We
anticipated a regio(halogen)selective Stille coupling with the
polyenylstannane 9 occurring at the alkenyl iodide end, which
would then be followed by the final Stille reaction at the
butenolide bromide position using alkenylstannane 6 (Figure
(7) Vaz, B.; Alvarez, R.; Bru¨ckner, R.; de Lera, A. R. Org. Lett. 2005,
7, 545.
(8) For other approaches to enantiopure peridinin 2, see the following:
(a) Furuichi, N.; Hara, H.; Osaki, T.; Mori, H.; Katsumura, S. Angew. Chem.
114, 1065; Angew. Chem., Int. Ed. 2002, 41, 1023. (b) Furuichi, N.; Hara,
H.; Osaki, T.; Takano, M.; Mori, H.; Katsumura, S. J. Org. Chem. 2004,
69, 7949-7959.
(9) This halogen-differentiated γ-alkylidenebutenolide was constructed
using a Mukaiyama aldol reaction followed by dehydration as described in
ref 7.
(5) Zeng, F.; Negishi, E. Org. Lett. 2001, 3, 719.
(6) Vaz, B.; Alvarez, R.; de Lera, A. R. J. Org. Chem. 2002, 67, 5040.
See the stereochemical correction in ref 24.
J. Org. Chem, Vol. 71, No. 16, 2006 5915

Vaz et al.
FIGURE 4. Retrosynthetic analysis of pyrrhoxanthin 1 using the dihalogenated C8-butenolide 7 as a linchpin.
SCHEME 1a
a(a) Pd(PPh3)4, K2CO3, DMF, 60 °C; (b) (n-Bu)4NF, THF, 25 °C, 4 h; (c) Ac2O, Py, 25 °C, 13 h, (89%, b-c); (d) Pd(PPh3)4, K2CO3, DMF, 60 °C (90%
for 16a, 76% for 16b); (e) BTSH, DIAD, PPh3, THF, -10 °C for 17a (98%; 10:1 E/Z); BTSH, DIAD, PPh3, THF, 25 °C for 17b (88%; 1.4:1 E/Z); (f) 35%
H2O2, (NH4)6Mo7O24‚4H2O, EtOH, 0 °C for 11a (65%).
4).10 Polyenylstannane 9 stood out as the only remaining frag-
ment for attempting the convergent sequential halogen-selective
Stille cross-coupling approach11 to pyrrhoxanthin 1. In exploiting
the greater stability of the Z isomers in this series, we conceived
that 9 could be obtained by a Z-selective Julia-Kocienski
olefination of â-stannylacrolein 10 and allyl benzothiazolyl-
(BT)-sulfone 11.7 This sulfone could in turn be acquired through
a cross-coupling reaction12 that combines either alkenyliodide
12 and enyne 1313 or cycloalkenyl triflate 1414 and enynol 15,
followed by the appropriate functional group transformations.
The former option was discarded following the observation that
coupling between 12 and 13 under Heck conditions [Pd(PPh3)4,
K2CO3, DMF] furnished only a mixture of isomers of the start-
ing allyl BT-sulfone 12 at ambient temperature and degradation
of the starting materials upon heating (up to 60 °C).
Enol triflate 14a15 derived from enantiopure actinol16 was
treated with enynol 15 under the reaction conditions indicated
above [Pd(PPh3)4, K2CO3, DMF, 60 °C] to afford the expected
alcohol 16a in good yield (90%). Mitsunobu-like BT-sulfide
formation (17a) and subsequent oxidation following the Ko-
cienski method17 transformed this alcohol into the corresponding
allyl BT-sulfone 11a (Scheme 1). Both processes required a
rigorous control of the temperature, which should not exceed
0 °C, to minimize the isomerization of the C9′-C10′ double
bond (carotenoid numbering).
(10) Fragment 6 has already been described in enantiopure form starting
from actinol through a sequence involving the preparation of an epoxycy-
clohexanol through a Sharpless asymmetric epoxidation, followed by Swern
oxidation, alkyne formation using Shioiri’s lithium diazomethane, and
palladium-assisted hydrostannation. See ref 7 for details.
(11) (a) Stille, J. K. Pure Appl. Chem. 1985, 57, 1771. (b) Stille, J. K.
Angew. Chem. 1986, 98, 504; Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(c) Farina, V. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Eds.; Elsevier: Oxford, U.K., 1995;
Vol. 12, Chapter 3.4, p 161. (d) Farina, V. Pure Appl. Chem. 1996, 68, 73.
(e) Farina, V.; Roth, G. P. In AdVances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; JAI Press: New York, 1996; Vol. 5, p 1. (f) Farina,
V.; Krishnamurthy, V.; Scott, W. J. Organic Reactions; Paquette, L. A.,
Ed.; John Wiley & Sons: 1997; Vol. 50, Chapter 1, p 1. (g) Duncton, M.
A. J.; Pattenden, G. J. Chem. Soc., Perkin Trans. 1 1999, 1235.
(12) Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998. Metal-catalyzed Cross-
coupling Reactions, 2nd. ed.; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, Germany, 2004.
(13) Enyne 13 was synthesized by coupling triflate 14a with TMS-
acetylene [Pd(PPh3)4, K2CO3, DMF, 60 °C, 93%) and alkyne desilylation
(K2CO3, MeOH, 25 °C, 2 h, 98%).
(14) (a) Ito, M.; Hirata, Y.; Shibata, Y.; Tsukida, K. J. Chem. Soc.,
Perkin Trans. 1 1990, 197. (b) Ito, M.; Yamano, Y.; Sumiya, S.; Wada, A.
Pure Appl. Chem. 1994, 66, 939. (c) Yamano, Y.; Tode, C.; Ito, M. J.
Chem. Soc., Perkin Trans. 1 1995, 1895.
(15) Nesnas, N.; Rando, R. R.; Nakanishi, K. Tetrahedron 2002, 58,
6577.
5916 J. Org. Chem., Vol. 71, No. 16, 2006

C37-Norcarotenoid Butenolide Pyrrhoxanthin
SCHEME 2a
is opposite to that required for natural pyrrhoxanthin 1, we
considered this to be inconsequential, since several methods that
induce the isomerization of a cis-polyene to the all-trans
geometry are known, including our observation that Stille
reaction conditions are efficient in this setting. At this stage
the hydroxyl group at C3′ of Z-9a was deprotected to Z-19 and
acetylated, affording the corresponding C18 polyenyl stannane
Z-9b (50% combined yield) required for the construction of the
C37 skeleton of pyrrhoxanthin 1.
The stage was now set for the connective Stille cross-coupling
reactions, under the optimized conditions developed in our
laboratory for carotenoid synthesis. Using Pd2(dba)3‚CHCl3 and
AsPh3 as catalyst in a thoroughly deoxygenated BHT-added
THF in the presence of tetrabutylammonium phosphinate25 Bu4-
NPh2PO2 as Bu3SnX scavenger, stannane Z-9b was coupled to
γ-alkylidenebutenolide 7 in an excellent yield (90%, Scheme
3). The geometry of the sole reaction product was determined
as corresponding to 9′Z-20 after careful analysis and interpreta-
tion of the NMR spectra (1H, COSY, HSQC) and nuclear
Overhauser effect (NOE) interactions (the most significant of
which are depicted in Figure 5). Additionally, the value of the
vicinal coupling constants for the vinyl protons across the double
bonds (between 14 and 14.5 Hz) confirmed the trans geometry
at the C11′-C14′ and C15′-C15 diene fragments. Given the
short reaction times and the mild temperatures used, the
occurrence of this highly selective double isomerization process
during a Stille coupling is quite remarkable. We surmise that
the isomerization could be due to ligand exchange processes at
palladium, involving the alkyne and neighboring olefins.
For the completion of the C37-norcarotenoid skeleton, cou-
pling of 9′Z-20 and alkenylstannane 6 provided 9′Z-1 as a single
isolable product in moderate yield (37%, Scheme 3). As in the
case of peridinin 2, the final step of the synthesis required
heating to 55 °C for extended periods (43 h) under the same
conditions indicated above, owing to the poor reactivity of 6.
The structure of the final carotenoid was established through
rigorous data analysis from ROESY experiments (Figure 5),
which confirmed in particular the 9′Z geometry as well as the
trans geometry of the remaining polyene bonds of the synthetic
9′Z-pyrrhoxanthin 9′Z-1.
a (a) NaHMDS, THF, -78 °C f 25 °C (78%); (b) (n-Bu)4NF, THF, 25
°C, 3 h; (c) Ac2O, Py, 25 °C, 4 h (50%, b-c).
Deprotection of allyl BT-sulphone 11a faced unanticipated
problems. Treatment with (n-Bu)4NF (THF, 25 °C, 1.5 h) led
to degradation, probably due to the basicity of the fluoride ion,
especially under anhydrous conditions,18 which appears to be
incompatible with the sensitive sulphone. The use of HF (48%
HF, pyridine, THF, 25 °C, 3.5 h) furnished the deprotected allyl
BT-sulfone, but with the undesired C9′-C10′ Z geometry.19
Alternative conditions were explored, but unfortunately either
complete or partial isomerization of the double bond of the
starting sulfone 11a resulted: PPTS/MeOH at 50 °C (only Z),20
CAN/MeOH at 0 °C (1:3 E/Z) or LiBF4/CH3CN (CH2Cl2, H2O,
25 °C, 40 h, only Z).21,22
Because of incompatibility of the various silyl ether depro-
tection conditions with the allyl BT-sulfone group or with its
geometrical integrity, the incorporation of the required acetate
was attempted earlier in the synthesis, thus avoiding manipula-
tion of unstable intermediates. Triflate 14a was desilylated
(TBAF, THF, 25 °C) and acetylated (Ac2O, Py, 25 °C, 89%
combined yield) to provide the substrate for the subsequent cross
coupling reaction with enynol 15 (Scheme 1). Despite the
success of this Pd catalyzed process (76% yield), the coupled
product 16b showed high geometrical instability, and isomer-
ization of the double bond under the Mitsunobu-type S-
alkylation conditions was observed (a 1.4:1 E/Z mixture of 17b
was obtained). The deprotection-acetylation of the secondary
alcohol was therefore postponed until a later stage in the
sequence.
In summary, the Julia-Stille-Stille sequence is a valuable
convergent approach to construct the complete skeleton of highly
functionalized acetylenic C37-norcarotenoid butenolides. The
palladium-induced isomerization, which proved beneficial during
the second Stille coupling in the case of peridinin 2, can be a
limitation, as shown in the present approach to pyrrhoxanthin
1. A double isomerization of a Z,E- to the E,Z-enyne occurs
during the first Stille coupling, despite the moderate tempera-
tures and relatively short reaction times employed, affording
the thermodynamically more stable C9′-Z-pyrrhoxanthin.26 This
feature represents an important drawback in the preparation of
unstable naturally occurring acetylenic carotenoids such as
pyrrhoxanthin 1 using Pd-catalyzed cross-coupling reactions.
Notwithstanding this limitation, our experience with polyenes
indicates that Pd-catalyzed processes represent a valuable
synthetic tool for the preparation of the adequate fragments for
carotenoid synthesis in an exquisite stereoselective manner. Our
efforts are now directed toward the stereoselective synthesis of
The synthesis of the enantiopure polyenylstannane 9 relied
on the precedented cis-selective (Sylvestre) Julia olefination
between allyl BT-sulfone 11a and â-stannylacrolein 10 which
uneventfully provided Z-9a.23 The Z > E stereoselectivity
resulting from the condensation of this (formally) allyl 2,6-dien-
4-yn-1-yl BT-sulfone (Scheme 2) confirms the general trend
exhibited by other allyl BT-sulfones in their condensation with
unsaturated aldehydes.24 Although the stereochemical outcome
(16) Yamano, Y.; Watanabe, Y.; Watanabe, N.; Ito, M. J. Chem. Soc.,
Perkin Trans. 1 2002, 2833.
(17) Blakemore, P. R.; Cole, W. J.; Kocienski, P.; Morley, A. Synlett
1998, 26.
(18) (a) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190. (b) Clark, J. H. Chem. ReV. 1980, 80, 429.
(19) Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 453.
(20) Prakash, C.; Saleh, S.; Blair, I. A. Tetrahedron Lett. 1989, 30, 19.
(21) (a) DattaGupta, A.; Singh, R.; Singh, V. K. Synlett 1996, 69. (b)
Hwu, J. R.; Jain, M. L.; Tsai, F.-Y.; Tsay, S.-C.; Balakumar, A.; Hakimelahi,
G. H. J. Org. Chem. 2000, 65, 5077.
(22) Metcalf, B. W.; Burkhart, K. P.; Jund, K. Tetrahedron Lett. 1980,
21, 35.
(23) The geometry of the polyenes was corroborated by 2D-NOESY
experiments.
(24) Vaz, B.; Alvarez, R.; Souto, J. A.; de Lera, A. R. Synlett 2005,
294.
(25) Srogl, J.; Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1997,
119, 12376.
(26) Bernhard, K.; Kienzle, F.; Mayer, H.; Mu¨ller, R: K. HelV. Chim.
Acta 1980, 63, 1473.
J. Org. Chem, Vol. 71, No. 16, 2006 5917

Vaz et al.
SCHEME 3a
a (a) Pd2(dba)3‚CHCl3, AsPh3, Bu4NPh2PO2, BHT, THF, 25 °C, 6.5 h (90%); (b) Pd2(dba)3‚CHCl3, AsPh3, Bu4NPh2PO2, BHT, THF, 55 °C, 43 h (37%).
raphy (90:10 hexane/ethyl acetate) to afford 0.949 g (89%) of a
colorless oil identified as (R)-4-acetoxy-2,6,6-trimethylcyclohex-
1-en-1-yl trifluoromethanesulfonate 14b. [R]26 -8.79 (c 0.264,
D
1
MeOH). H NMR (400 MHz, CDCl3): δ 5.1-4.9 (m, 1H), 2.53
(dd, J ) 17.0, 5.7 Hz, 1H), 2.19 (dd, J ) 17.0, 8.6 Hz, 1H), 2.00
(s, 3H), 1.9-1.8 (m, 1H), 1.8-1.7 (m, 1H), 1.72 (s, 3H), 1.20 (s,
3H), 1.14 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 170.4 (s),
1
148.8 (s), 123.2 (s), 118.7 (q, JC-F ) 319.7 Hz), 66.4 (d), 44.4
(t), 37.2 (t), 36.4 (s), 27.0 (q), 26.5 (q), 21.1 (q), 17.4 (q) ppm. MS
(EI+) m/z (%): 353 (M+ + 23, 78), 348 (12), 332 (M+ + 2, 12),
331 (M+ + 1, 100), 271 (13). HRMS (EI+): Calcd for C12H18F3O5S,
331.0821; found, 331.0822.
(1R,3′E)-4-(5-Hydroxy-3-methylpent-3-en-1-yn-1-yl)-3,5,5-tri-
methylcyclohex-3-en-1-yl Acetate 16b. To a solution of (R)-4-
acetoxy-2,6,6-trimethylcyclohex-1-en-1-yl trifluoromethanesulfonate
14b (0.804 g, 2.43 mmol) in DMF (29 mL) was added Pd(PPh3)4
FIGURE 5. NOEs for 9′Z-20 and 9′Z-pyrrhoxanthin 9′Z-1 extracted
from the NOESY spectra. The intensities are indicated as s (strong >
7%), m (medium, 3-7%), and w (weak, < 3%).
(0.18 g, 0.24 mmol) and K2CO3 (1.01 g, 7.30 mmol). After addition
of 3-methylpent-2-en-4-yn-1-ol 15 (0.444 g, 4.62 mmol), the
reaction mixture was stirred at 60 °C for 6 h. The mixture was
diluted with Et2O, and the layers were separated. The aqueous layer
was washed with H2O (3x), the combined organic layers were dried
(Na2SO4), and the solvent was evaporated. The residue was purified
by column chromatography (80:20 hexane/ethyl acetate) to afford
0.514 g (76%) of a colorless oil identified as (1R,3′E)-4-(5-hydroxy-
all-trans pyrrhoxanthin 1, avoiding the use of palladium catalysts
during the late stages of the sequence and ensuring the stereo-
controlled preparation of these very unstable and highly func-
tionalized carotenoids.
3-methylpent-3-en-1-yn-1-yl)-3,5,5-trimethylcyclohex-3-en-1-yl ac-
Experimental Section.
1
etate 16b. [R]26 -47.39 (c 0.34, MeOH). H NMR (400 MHz,
D
(CD3)2CO): δ 5.94 (t, J ) 6.5 Hz, 1H), 5.1-4.9 (m, 1H), 4.19 (t,
J ) 5.9 Hz, 2H), 3.73 (t, J ) 5.5 Hz, 1H), 2.47 (dd, J ) 17.7, 5.5
Hz, 1H), 2.14 (dd, J ) 17.8, 9.1 Hz, 1H), 2.00 (s, 3H), 1.89 (s,
3H), 1.85 (s, 3H), 1.9-1.8 (m, 1H), 1.55 (t, J ) 11.8 Hz, 1H),
1.19 (s, 3H), 1.16 (s, 3H) ppm. 13C NMR (100 MHz, (CD3)2CO):
δ 169.5 (s), 136.2 (s), 136.1 (d), 123.7 (s), 119.0 (s), 96.3 (s), 84.6
(s), 67.1 (d), 58.0 (t), 42.0 (t), 36.9 (t), 35.6 (s), 29.5 (q), 27.9 (q),
(R)-4-Acetoxy-2,6,6-trimethylcyclohex-1-en-1-yl Trifluoro-
methanesulfonate 14b. To a solution of (R)-4-(tert-butyldimethyl-
silyloxy)-2,6,6-trimethylcyclohex-1-en-1-yl trifluoromethanesulfonate
14a (1.30 g, 3.23 mmol) in THF (30 mL) was added (n-Bu)4NF
(4.85 mL, 4.85 mmol), and the mixture was stirred at 25 °C for 4
h. The reaction mixture was poured into a saturated NaHCO3
solution and extracted with Et2O (3x). The combined organic layers
were dried (Na2SO4), and the solvent was evaporated. The residue
was used in the next step without further purification. To a solution
of this residue in pyridine (10 mL) was added Ac2O (1.51 mL,
16.17 mmol). After stirring at 25 °C for 13 h, the mixture was
diluted with t-BuOMe (3x) and washed with a saturated CuSO4
solution (2x). The organic layer was dried (Na2SO4), and the solvent
was evaporated. The residue was purified by column chromatog-
21.4 (q), 20.1 (q), 16.8 (q) ppm. MS (EI+) m/z (%): 299 (M+
+
23, 100), 199 (51). HRMS (EI+): Calcd for C17H24NaO3, 299.1618;
found, 299.1619.
(-)-(2E,4′R)-5-(4-tert-Butyldimethylsilyloxy-2,6,6-trimethyl-
cyclohex-1-en-1-yl)-3-methylpent-2-en-4-yn-1-ol 16a. To a solu-
tion of (R)-4-(tert-butyldimethylsilyloxy)-2,6,6-trimethylcyclohex-
1-en-1-yl trifluoromethanesulfonate 14a (0.50 g, 1.25 mmol) in
5918 J. Org. Chem., Vol. 71, No. 16, 2006

C37-Norcarotenoid Butenolide Pyrrhoxanthin
DMF (15 mL) was added Pd(PPh3)4 (0.14 g, 0.12 mmol) and K2-
CO3 (0.52 g, 3.73 mmol). After the addition of 3-methylpent-2-
en-4-yn-1-ol 15 (0.36 mL, 3.73 mmol), the reaction mixture was
stirred at 60 °C for 6 h. The mixture was diluted with Et2O, and
the layers were separated. The aqueous layer was washed with H2O
(3x), the combined organic layers were dried (Na2SO4), and the
solvent was evaporated. The residue was purified by column
chromatography (80:20 hexane/ethyl acetate) to afford 0.073 g
(98%) of a colorless oil identified as (-)-(2E,4′R)-5-(4-tert-
butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methyl-
pent-2-en-4-yn-1-ol 16a. [R]26D -78.36 (c 0.16, CHCl3). 1H NMR
(400 MHz, (CD3)2CO): δ 5.82 (tq, J ) 6.5 and 1.3 Hz, 1H), 4.08
(t, J ) 6.5 Hz, 2H), 3.9-3.8 (m, 1H), 2.23 (ddd, J ) 17.7, 5.4, 1.4
Hz, 1H), 1.95 (ddd, J ) 17.7 Hz, 9.3, 1.4 Hz, 1H), 1.77 (s, 3H),
1.74 (d, J ) 1.3 Hz, 3H), 1.64 (ddd, J ) 12.0, 3.5, 1.9 Hz, 1H),
1.33 (t, J ) 12.0 Hz, 1H), 1.06 (s, 3H), 1.03 (s, 3H), 0.81 (s, 9H),
0.00 (s, 6H) ppm. 13C NMR (100 MHz, (CD3)2CO): δ 138.6 (s),
137.3 (d), 124.9 (s), 120.5 (s), 97.5 (s), 86.4 (s), 66.5 (d), 59.4 (t),
48.2 (t), 42.9 (t), 37.4 (s), 31.2 (q), 29.4 (q), 26.6 (q, 3x), 22.9 (q),
19.0 (s), 18.2 (q), -4.1 (q, 2x) ppm. MS (EI+) m/z (%): 348 (M+,
4), 291 (17), 273 (38), 235 (65), 218 (19), 217 (100), 157 (15),
143 (18), 75 (23). HRMS (EI+): Calcd for C21H36O2Si, 348.2485;
found, 348.2473. FT-IR (NaCl): ν 3600-3100 (br, OH), 2950 (s,
C-H), 2928 (s, C-H), 2857 (s, C-H), 1469 (m), 1377 (m), 1253
(m), 1086 (s, Si-O), 836 (m) cm-1
solid identified as (2E,4′R)-1-(benzothiazol-2-yl)sulfonyl-5-(4-tert-
butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methyl-
1
pent-2-en-4-yne 11a. E-11a: [R]26 -25.12 (c 0.23, MeOH). H
D
NMR (600 MHz, CDCl3): δ 8.19 (d, J ) 8.1 Hz, 1H), 7.98 (d, J
) 8.1 Hz, 1H), 7.58 (m, 2H), 5.74 (t, J ) 8.1 Hz, 1H), 4.31 (d, J
) 8.2 Hz, 2H), 3.9-3.8 (m, 1H), 2.21 (dd, J ) 17.7, 5.3 Hz, 1H′),
2.02 (dd, J ) 17.8, 9.3 Hz, 1H), 1.79 (s, 3H), 1.78 (s, 3H), 1.65 (d,
J ) 12.6 Hz, 1H), 1.39 (t, J ) 12.1 Hz, 1H), 1.06 (s, 3H), 1.03 (s,
3H), 0.85 (s, 9H), 0.03 (s, 6H) ppm. 13C NMR (150 MHz, CDCl3):
δ 165.7 (s), 152.6 (s), 139.7 (s′), 137.1 (s), 129.4 (s), 128.0 (d),
127.6 (d), 125.4 (d), 123.3 (s), 122.3 (d), 117.7 (d), 94.9 (s), 89.1
(s), 65.3 (d), 54.9 (t), 46.9 (t′), 42.0 (t), 36.4 (s), 30.3 (q), 28.6 (q),
25.9 (q, 3x), 22.4 (q), 18.3 (q), 18.2 (s), -4.7 (q), -4.6 (q) ppm.
MS (EI+) m/z (%): 529 (M+, 1), 332 (28), 331 (100), 200 (16),
199 (90), 174 (10), 173 (68), 157 (12), 143 (16), 75 (18), 73 (28).
HRMS (EI+): Calcd for C24H30NO3S2Si, 472.1436; found, 472.1424.
FT-IR (NaCl): ν 2956 (s, C-H), 2928 (s, C-H), 2856 (s, C-H),
2186 (m, CtC), 1612 (w), 1473 (s), 1334 (s), 1146 (s), 1085 (s)
cm-1. Anal. Calcd for C28H39NO3S2Si: C, 63.47; H, 7.42; N, 2.64;
S, 12.10. Found: C, 63.20; H, 7.39; N, 2.69; S, 12.05.
Z-11a: 1H NMR (600 MHz, CDCl3): δ 8.18 (d, J ) 8.0 Hz,
1H), 8.00 (d, J ) 8.1 Hz, 1H), 7.60 (m, 2H), 5.70 (t, J ) 7.6 Hz,
1H), 4.47 (d, J ) 7.6 Hz, 2H), 3.9-3.8 (m, 1H), 2.25 (dd, J )
17.7, 5.2 Hz, 1H), 2.05 (dd, J ) 17.7, 9.3 Hz, 1H), 1.94 (s, 3H),
1.79 (s, 3H), 1.67 (d, J ) 12.4 Hz, 1H), 1.40 (t, J ) 12.1 Hz, 1H),
1.02 (s, 3H), 1.00 (s, 3H), 0.91 (s, 9H), 0.08 (s, 6H) ppm. 13C NMR
(150 MHz, CDCl3): δ 165.3 (s), 152.7 (s), 140.1 (s′), 137.3 (s),
129.9 (s), 127.9 (d), 127.4 (d), 125.6 (d), 123.2 (s), 122.2 (d), 117.8
(d), 94.9 (s), 90.7 (s), 65.2 (d), 57.4 (t), 46.9 (t), 42.1 (t), 36.3 (s),
30.4 (q), 28.6 (q), 25.9 (q, 3x), 23.8 (q), 22.6 (q), 18.2 (s), -4.6
(q, 2x) ppm. MS (FAB+) m/z (%): 529 (M++1, 11), 332 (32),
331 (100), 286 (16), 215 (16), 200 (20), 199 (70), 189 (17), 180
(16), 178 (17), 173 (46), 169 (16), 167 (20), 166 (17), 165 (29),
157 (18), 155 (24), 154 (65). HRMS (FAB+): Calcd for C28H40-
NO3SiS2, 530.2219; found, 530.2209. FT-IR (NaCl): ν 2956 (s,
C-H), 2928 (s, C-H), 2856 (s, C-H), 2184 (m, CtC), 1612 (w),
1471 (s), 1335 (s), 1146 (s), 1085 (s) cm-1. Anal. Calcd for C28H39-
NO3SiS2: C, 63.47; H, 7.42; N, 2.64; S, 12.10. Found: C, 63.21;
H, 7.39; N, 2.60; S, 11.94.
(-)-(2E,4′R)-1-(Benzothiazol-2-yl)sulfanyl-5-(4-tert-butyldi-
methylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methylpent-
2-en-4-yne 17a. A solution of diisopropyl azodicarboxylate (DIAD,
0.083 mL, 0.43 mmol) and PPh3 (0.123 g, 0.47 mmol), in THF (1
mL) was stirred at -10 °C for 5 min. A solution of (2E,4′R)-5-
(4-terc-butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-
3-methylpent-2-en-4-yn-1-ol 16a (0.10 g, 0.29 mmol) in THF
(1 mL) and 2-mercaptobenzothiazole (0.07 g, 0.43 mmol) were
added, and the resulting mixture was stirred at -10 °C for 2 h.
The solvent was evaporated, and the residue was purified by chro-
matography (96:2:2 hexane/ethyl acetate/Et3N) to afford 0.14 g
(98%) of a colorless oil identified as (-)-(2E,4′R)-1-(benzothiazol-
2-yl)sulfanyl-5-(4-tert-butyldimethylsilyloxy-2,6,6-trimethylcyclo-
hex-1-en-1-yl)-3-methylpent-2-en-4-yne 17a. [R]25D -85.58 (c 0.03,
CHCl3). 1H NMR (400 MHz, (CD3)2CO): δ 7.95 (dd, J ) 8.0, 0.5
Hz, 1H), 7.86 (dd, J ) 8.1, 0.5 Hz, 1H), 7.48 (ddd, J ) 8.1, 7.3,
1.2 Hz, 1H), 7.37 (ddd, J ) 8.0, 7.3, 1.2 Hz, 1H), 6.04 (td, J )
8.0, 1.5 Hz, 1H), 4.21 (d, J ) 8.0 Hz, 2H), 4.0-3.9 (m, 1H), 2.31
(ddd, J ) 17.7, 5.6, 1.3 Hz, 1H), 2.04 (s, 3H), 2.00 (m, 1H), 1.85
(s, 3H), 1.73 (ddd, J ) 12.6, 3.5, 2.0 Hz, 1H), 1.41 (t, J ) 12.0
Hz, 1H), 1.14 (s, 3H), 1.10 (s, 3H), 0.90 (s, 9H), 0.09 (s, 6H) ppm.
13C NMR (100 MHz, (CD3)2CO): δ 166.8 (s), 154.3 (s), 139.1
(s), 136.3 (s), 130.1 (d), 127.2 (d), 125.5 (d), 124.4 (s), 124.3 (s),
122.4 (d), 122.3 (d), 96.8 (s), 87.9 (s), 66.1 (d), 47.9 (t), 42.6 (t),
37.1 (s), 31.9 (t), 30.9 (q), 29.0 (q), 26.3 (q, 3x), 22.7 (q), 18.7 (s),
18.2 (q), -4.4 (q, 2x) ppm. MS (EI+) m/z (%): 499 (M+ + 2, 8),
498 (M+ + 1, 16), 497 (M+, 42), 332 (14), 331 (48), 330 (13), 199
(36), 174 (14), 173 (100), 157 (15), 143 (21), 129 (11), 75 (27), 73
(43). HRMS (EI+): Calcd for C28H39OS2Si, 497.2242; found,
497.2238. FT-IR (NaCl): ν 2956 (s, C-H), 2921 (s, C-H), 2856
(s, C-H), 2186 (w, CdC), 1460 (s), 1427 (s), 1083 (s, Si-O),
(R)-tert-Butyldimethylsilyl 4-[(3′E,5′Z,7′E)-3-Methyl-8-(tri-
butylstannyl)octa-3,5,7-trien-1-yn-1-yl]-3,5,5-trimethylcyclohex-
3-en-1-yl Ether 11′Z-9a. To a solution of (2E,4′R)-1-(benzothiazol-
2-yl)sulfanyl-5-[4-tert-butyldimethylsilyloxy-2,6,6-trimethylcyclohex-
1-en-1-yl]-3-methylpent-2-en-4-yne 11a (0.045 g, 0.085 mmol) in
THF (4 mL), was added NaHMDS (0.25 mL, 1 M in THF, 0.25
mmol), and the reaction mixture was stirred for 30 min. A solution
of 3-tri-n-butylstannylpropen-1-al 10 (0.044 g, 0.13 mmol) in THF
(2 mL) was added, and the reaction mixture was stirred for 2 h.
H2O was slowly added, and the reaction mixture was allowed to
reach ambient temperature. It was then diluted with Et2O, and the
separated aqueous layer was further extracted with Et2O (3x). The
combined organic layers were dried (Na2SO4), and the solvent was
removed. The residue was purified by chromatography (C-18
silicagel, 80:20 CH3CN/CH2Cl2), to afford 53.2 mg (78%) of a
yellow oil identified as (R)-tert-butyldimethylsilyl 4-[(3′E,5′Z,7′E)-
3-methyl-8-(tributystannyl)octa-3,5,7-trien-1-yn-1-yl]-3,5,5-trimeth-
996 (m) cm-1
.
1
ylcyclohex-3-en-1-yl ether 11′Z-9a. H NMR (400 MHz, C6D6):
(2E,4′R)-1-(Benzothiazol-2-yl)sulfanyl-5-(4-tert-butyldimethyl-
silyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methylpent-2-en-
4-yne 11a. To a solution of (2E,4′R)-1-(benzothiazol-2-yl)sulfanyl-
5-(4-tert-butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)-
3-methylpent-2-en-4-yne 17a (0.20 g, 0.40 mmol) in EtOH (5 mL),
at 0 °C, was added a solution of (NH4)6Mo7O24‚4H2O, (0.05 g,
0.04 mmol) in aqueous hydrogen peroxide (35%, 0.60 mL, 2.0
mmol). After stirring for 48 h, the mixture was quenched with brine
and extracted with Et2O (3x). The combined organic layers were
washed with brine (2x) and dried (Na2SO4), and the solvent was
removed. The residue was purified by chromatography (silicagel,
85:12:3 hexane/EtOAc/Et3N) to afford 0.14 g (65%) of a white
δ 7.36 (dd, J ) 18.5, 10.8 Hz, 1H), 7.0-6.9 (m, 2H), 6.47 (d, J )
18.5 Hz, 1H), 6.19 (t, J ) 9.5 Hz, 1H), 4.0-3.8 (m, 1H), 2.24 (dd,
J ) 17.8, 5.3 Hz, 1H), 2.12 (dd, J ) 17.8, 9.2 Hz, 1H), 1.90 (s,
3H), 1.88 (s, 3H), 1.78 (ddd, J ) 12.6, 3.3, 1.7 Hz, 1H), 1.7-1.5
(m, 7H), 1.4-1.3 (m, 6H), 1.31 (s, 3H), 1.23 (s, 3H), 1.1-1.0 (m,
15H), 1.0-0.9 (m, 9H), 0.09 (s, 3H), 0.08 (s, 3H) ppm. 13C NMR
(100 MHz, (C6D6): δ 142.3 (d), 138.2 (s), 136.3 (d), 132.3 (d),
129.8 (d), 126.5 (d), 124.2 (s), 121.5 (s), 95.4 (s), 93.6 (s), 65.4
(d), 47.2 (t), 42.1 (t), 36.4 (s), 30.5 (q, 3x), 29.2 (t, 3x 3JSn ) 10.4
Hz), 28.6 (q), 27.3 (t, 3x), 25.7 (q, 3x), 23.6 (q), 22.4 (q), 18.0 (s),
13.5 (q, 3x), 9.5 (t, 3x), -4.8 (q, 2x) ppm. MS (FAB+) m/z (%):
660 (M+ + 2, 13), 659 (M+ + 1, 13), 658 (M+ + 1, 12), 604 (27),
J. Org. Chem, Vol. 71, No. 16, 2006 5919

Vaz et al.
603 (67), 602 (34), 601 (51), 600 (25), 599 (27), 547 (28), 545
(39), 543 (26), 369 (22), 291 (69), 290 (26), 289 (56), 288 (22),
287 (34), 237 (34), 235 (63), 234 (23), 233 (48), 231 (30), 195
(24), 193 (22), 183 (22), 181 (28), 179 (100), 178 (32), 177 (93),
176 (31), 175 (62). HRMS (EI+): calcd for C36H65OSi116Sn,
657.3821; found, 659.3851; calcd for C36H65OSi118Sn, 659.3827;
found, 661.3817; calcd for C36H65OSi120Sn, 661.3827; found,
661.3817.
J ) 14.4, 10.9 Hz, 1H), 6.41 (d, J ) 10.8 Hz, 1H), 6.10 (s, 1H),
5.2-5.0 (m, 1H), 2.52 (dd, J ) 17.9, 5.5 Hz, 1H), 2.21 (s, 3H),
2.2-2.1 (m, 1H), 2.00 (s, 6H, C9′-CH3), 1.96 (s, 3H), 1.87 (ddd, J
) 12.4, 3.5, 1.8 Hz, 1H), 1.58 (t, J ) 11.8 Hz, 1H), 1.24 (s, 3H),
1.21 (s, 3H) ppm. 13C NMR (100 MHz, (CD3)2CO): δ 171.6 (s),
167.0 (s), 148.4 (s), 145.3 (d), 141.2 (d), 139.7 (d), 136.7 (d), 135.3
(d, 2x), 134.6 (s), 132.2 (s), 131.6 (d), 125.9 (s), 123.6 (s), 121.7
(d), 110.4 (s), 110.2 (s), 97.3 (s), 69.1 (d), 44.0 (t), 39.1 (t), 37.7
(s), 31.7 (q), 30.1 (q), 24.8 (q), 23.7 (q), 22.2 (q), 16.3 (q) ppm.
MS (FAB+) m/z (%): 513 (M+ -Ac + 1, 57), 512 (M+ -Ac, 100),
511 (M+ -Ac - 1, 58), 510 (M+ -Ac, 90), 461 (34), 460 (63), 453
(1R,3′E,5′Z,7′E)-4-[3-Methylocta-8-(tributylstannyl)-3,5,7-
trien-1-yn-1-yl]-3,5,5-trimethylcyclohex-3-enyl Acetate Z-19. A
solution of (R)-tert-butyldimethylsilyl 4-[(3E,5Z,7E)-3-methyl-8-
(tributylstannyl)octa-3,5,7-trien-1-yn-1-yl]-3,5,5-trimethylcyclohex-
3-en-1-yl ether Z-9a (0.51 g, 0.078 mmol) in THF (1 mL) was
treated with nBu4NF (0.12 mL, 0.12 mmol), and the mixture was
stirred at 25 °C for 2 h. It was then poured over an aqueous saturated
NaHCO3 solution and extracted with AcOEt (3x). The residue was
used in the next step without purification. Acetic anhydride (0.036
mL, 0.39 mmol) was added to a solution of the residue above in
pyridine (1 mL). After being stirred for 16 h at ambient temperature,
EtOAc was added and the mixture was washed with a saturated
CuSO4 solution (2x), dried (Na2SO4), and the solvent was removed.
The residue was purified by chromatography (silicagel, hexane/
EtOAc/Et3N 90:10:0 f 77:20:3 gradient), to afford 0.016 g (50%)
of a yellow oil identified as (1R,3′E,5′Z,7′E)-4-[3-methylocta-8-
(tributylstannyl)-3,5,7-trien-1-yn-1-yl]-3,5,5-trimethylcyclohex-3-
en-1-yl acetate Z-9b and 0.011 g (0.017 mmol) of starting material
Z-9a. 1H NMR (400 MHz, C6D6): δ 7.36 (dd, J ) 18.5, 10.8 Hz,
1H), 6.9-6.8 (m, 2H), 6.48 (d, J ) 18.5 Hz, 1H), 6.2-6.1 (m,
1H), 5.4-5.2 (m, 1H), 2.31 (dd, J ) 17.7, 5.4 Hz, 1H), 1.97 (dd,
J ) 17.8, 9.1 Hz, 1H), 1.87 (s, 3H), 1.80 (s, 3H), 1.8-1.7 (m,
1H), 1.71 (s, 3H), 1.7-1.6 (m, 6H), 1.6-1.5 (m, 1H), 1.4-1.3 (m,
6H), 1.26 (s, 3H3), 1.22 (s, 3H), 1.1-1.0 (m, 6H), 1.0-0.9 (m,
9H) ppm. 13C NMR (100 MHz, C6D6): δ 169.3 (s), 142.3 (d), 137.0
(s), 136.5 (d), 132.4 (d), 130.0 (d), 126.4 (d), 124.4 (s), 121.4 (s),
95.0 (s), 93.7 (s), 67.4 (d), 42.3 (t), 37.3 (t), 35.9 (s), 30.1 (q), 29.2
(t, 3x, 3JSn-C ) 10.4 Hz), 28.5 (q), 27.3 (t, 3x, 2JSn-C ) 27.4 Hz),
23.5 (q), 22.1 (q), 20.5 (q), 13.5 (q, 3x), 9.5 (t, 3x) ppm. MS (FAB+)
m/z (%): 535 (M+ -Bu, 6), 533 (M+ -Bu, 7), 532 (M+ -Bu, 11),
531 (M+ -Bu, 35), 530 (M+ -Bu, 17), 529 (M+ -Bu, 28), 528 (M+
-Bu, 14), 527 (M+ -Bu, 17), 471 (26), 357 (24), 355 (24), 297 (20),
295 (36), 293 (79), 292 (30), 291 (100), 290 (38), 289 (72), 287
(29), 239 (41), 238 (39), 237 (79), 235 (85), 234 (30), 233 (62),
232 (24), 231 (37), 223 (27), 222 (30), 221 (99), 207 (49), 205
(22), 193 (25), 191 (25), 179 (62), 177 (61), 175 (40). HRMS
(EI+): Calcd for C28H43O2116Sn, 527.2280; found, 527.2297; calcd
for C28H43O2118Sn, 529.2279; found, 529.2255; calcd for C28H43O2-
120Sn, 531.2285; found, 531.2289.
(37), 451 (40), 327 (55), 325 (34), 309 (38). HRMS (IE+): Calcd
81
for C28H3179BrO4, 510.1406; found, 510.1394; calcd for C28H31
-
BrO4, 512.1385; found, 512.1379.
9′Z-Pyrrhoxanthin 9′Z-1. To a solution of Pd2(dba)3‚CHCl3
(0.001 g, 0.001 mmol) in THF (0.5 mL) was added AsPh3 (0.002 g,
0.008 mmol). After stirring at 25 °C for 5 min, a solution of 9′Z-20
(0.010 g, 0.020 mmol) was added, and the mixture was stirred for
at 25 °C for 10 min. A solution of tributyl{(1E,1′S,6′R)-2-(2,2,6-
trimethyl-7-oxa-bicyclo[4.1.0]heptan-1-yl)vinyl}stannane 6 (0.011
g, 0.020 mmol) in THF (1.0 mL) and Bu4NPh2PO2 (0.009 g, 0.020
mmol) were added, and the reaction was thoroughly degassed using
freeze-thaw cycles (3x). After being stirred at 55 °C for 43 h,
brine was added and the mixture was extracted with EtOAc/CH2-
Cl2 (90:10) (3x). The combined organic layers were dried (Na2-
SO4), and the solvent was removed. The residue was purified by
chromatography (silicagel, 67:20:3 hexane/acetone/Et3N), to afford
4.5 mg (37%) of a red solid identified as 9′Z-pyrroxanthin 9′Z-1.
1H NMR (600 MHz, CDCl3): δ 7.16 (d, J ) 15.6 Hz, 1H), 7.01
(s, 1H), 6.79 (dd, J ) 14.4, 11.3 Hz, 1H), 6.61 (dd, J ) 13.8, 11.6
Hz, 1H), 6.46 (d, J ) 11.1 Hz, 1H), 6.45 (dd, J ) 14.3, 12.1 Hz,
1H), 6.4-6.3 (m, 1H), 6.36 (d, J ) 15.5 Hz, 1H), 6.28 (d, J )
11.1 Hz, 1H), 5.71 (s, 1H), 5.2-5.0 (m, 1H), 4.0-3.8 (m, 1H),
2.52 (dd, J ) 17.5, 5.5 Hz, 1H), 2.39 (ddd, J ) 14.3, 5.0, 1.6 Hz,
1H), 2.21 (s, 3H), 2.15 (dd, J ) 17.3, 9.4 Hz, 1H), 2.04 (s, 3H),
2.00 (s, 3H), 1.94 (s, 3H), 1.85 (ddd, J ) 12.5, 3.4, 1.6 Hz, 1H′),
1.7-1.6 (m, 3H), 1.3-1.2 (m, 1H), 1.21 (s, 3H), 1.20 (s, 3H), 1.19
(s, 6H), 0.96 (s, 3H) ppm. 13C NMR (100 MHz, C6D6): δ 170.7
(s), 168.7 (s), 146.8 (s), 137.9 (d), 137.5 (s), 137.1 (d), 136.3 (d),
134.8 (d), 134.1 (s), 133.7 (d), 133.4 (d), 132.9 (d), 129.4 (d5),
124.9 (s), 124.3 (s), 121.9 (s), 121.8 (d), 119.1 (d), 95.4 (s), 94.0
(s), 70.4 (s), 67.9 (d), 67.5 (s), 64.2 (d), 47.1 (t), 42.3 (t′), 40.9 (t),
37.6 (t), 36.1 (s), 35.3 (s), 30.3 (q), 29.5 (q), 28.8 (q), 24.9 (q),
23.8 (q), 22.5 (q), 21.4 (q), 19.9 (q), 15.4 (q) ppm. MS (EI+) m/z
(%): 636 (M+ + 24, 37), 635 (M+ + 23, 89), 614 (M+ + 2, 44),
613 (M+ + 1, 100), 539 (20), 451 (24), 391 (29), 315 (48), 279
(45). HRMS (EI+): Calcd for C39H49O6, 613.3524; found, 613.3511;
calcd for C39H48NaO6, 635.3343; found, 635.3327.
9′Z-20. To a solution of Pd2(dba)3‚CHCl3 (5 × 10-4 g, 0.005
mmol) in THF (0.3 mL) was added AsPh3 (0.001 g, 0.004 mmol).
After stirring for 5 min at 25 °C, (5Z,1′E)-3-bromo-5-(3-iodo-2-
methyl-propenyliden)-5H-furan-2-one 7 (0.008 g, 0.023 mmol) was
added, and the mixture was stirred for 10 min at 25 °C. A solution
of (1R,3′E,5′Z,7′E)-4-[3-methylocta-8-(tributylstannyl)-3,5,7-trien-
1-yn-1-yl]-3,5,5-trimethylcyclohex-3-en-1-yl acetate Z-9b (0.016
g, 0.028 mmol) in THF (0.3 mL) and Bu4NPh2PO2 (0.011 g, 0.023
mmol) were added, and the reaction mixture was stirred for at 25
°C for 6.5 h. Brine was added, and the mixture was extracted with
EtOAc/CH2Cl2 (90:10) (3x). The combined organic layers were
dried (Na2SO4), and the solvent was removed. The residue was
purified by chromatography (silicagel, hexane/EtOAc 60:40 f 50:
50 gradient), to afford 10.5 mg (90%) of a red solid identified as
9′Z-20. 1H NMR (600 MHz, (CD3)2CO): δ 7.93 (s, 1H), 6.87 (dd,
J ) 14.5, 11.4 Hz, 1H), 6.79 (dd, J ) 14.0, 11.9 Hz, 1H), 6.66
(d, J ) 11.9 Hz, 1H), 6.62 (dd, J ) 14.0, 11.5 Hz, 1H), 6.55 (dd,
Acknowledgment. We thank the European Commission
(EPITRON, Contract No. 518417), the Spanish Ministerio de
Ciencia y Tecnolog´ıa (Grant SAF04-07131-FEDER and FPU
fellowship to B.V. and M.D.), and Xunta de Galicia (Grant
PGIDIT05PXIC31403PN) for financial support. We also thank
Dr. Michelangelo Scalone (F. Hoffman-La Roche, Basel) for a
generous gift of enantiopure actinol and Prof. R. Bru¨ckner for
stimulating discussions.
Supporting Information Available: Physical and spectroscopic
data of all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO060490Z
5920 J. Org. Chem., Vol. 71, No. 16, 2006